In recent years, various nucleic acid analogs have been synthesized with an aim to use a nucleic acid molecule as a pharmaceutical or functional molecule. Among them, 2′-modified type nucleic acid exhibits improved double strand-forming ability and enzyme resistance by conducting an appropriate chemical modification, and is known to be a useful chemical modified-type nucleic acid.
Among the 2′-modified type nucleic acids, the 2′-O-methyl-modified body is the simplest 2′-O-alkyl type of the modified body. Non-Patent document 1 (Inoue, H; Miura, K.; Ohtsuka, E. et al, G Nucleic Acid Res., 1987, 15, 6131-6148) suggests that 2′-O-methyl modification (O*—CH3) of the nucleic acid can improve the Tm value. On the other hand, Non-Patent Document 2 (Saneyoshi, H.; Seio, K.; Sekine, M., J. Org. Chem. 2005, 70, 10453-10460) describes that when 2′-O-Me modification is conducted at only one nucleic acid, the Tm value decreases.
JP 2009-256335 A (Patent document 1 described below) discloses a method of manufacturing a ribonucleic acid that has an alkyl type-protective group at the 2′ position.
In addition, Non-Patent Document 3 (Martin, P., Helv. Chim. Acta., 1995, 78, 486-504) discloses a 2′-O-methoxyethyl-modified body (O*—C2H4OCH3).
Most of the 2′-modified type RNAs including the 2′-O-methyl-modified body or the 2′-O-methoxyethyl-modified body mentioned above have a trouble in the introduction depending on the kind of the nucleic acid base. In other words, as for the 2′-O-methyl-modified body and the 2′-O-methoxyethyl-modified body, synthesis examples of only the RNA modified bodies having the pyrimidine nucleic acid base have been reported. In addition, it is necessary to search for an appropriate manufacturing method in which a synthesis method is changed depending on the kind of the nucleic acid base when these modified bodies are manufactured.
Non-Patent Document 4 (Tereshko, V.; Portmann, S.; Tay, E.; Martin, P; Natt, F.; Altmann, K.; Egli, M. Biochemistry, 1998, 37, 10626-10634) discloses a 2′-O-ethoxymethyl-modified body (O*—CH2OC2H5). However, if the 2′-O-ethoxymethyl modification is performed, the double strand melting temperature is lowered. In other words, the 2′-O-ethoxymethyl-modified body has a low double strand-forming ability. For this reason, it has been considered that the 2′-O-ethoxymethyl-modified body is not useful as a modified body of RNA.